The overall goal of this project is to gain a better understanding of the mechanism(s) that regulates DNA synthesis, mitosis and tissue repair in the mammalian lens. We also hope to gain additional insight into the mechanism by which transparency and tissue organization are reestablished in the traumatized lens. Such data may have significance in ophthalmology and in other fields of the bio-medical sciences in which the mechanism which controls cell divison and growth plays an important role. Mitosis in the cultured rabbit lens can be initiated by the addition of insulin, serum or certain aqueous humors to completely defined medium. The specific aims are to: identify the mitogenic factors in aqueous humor; isolate and evaluate the mitogenicity of insulin-like factors from serum; determine the components in the culture medium that act in concert with the factor(s) to permit DNA synthesis and mitosis in the rabbit lens of organ culture and in human lens epithelium. We plan to determine the localization of insulin receptor. Attention will also focus upon any changes (e.g., changes in macromolecular synthesis, i.e., RNA and protein synthesis and morphological changes at the electron microscope level) that may characterize the newly stimulated cells. Changes in the localization and magnitude of the reaction products for acid and alkaline phosphatase, ATPase, phosphodiesterase, and in cell surface mucopolysaccharides will be evaluated by the use of cytochemical techniques at the ultrastructural level. Concomitant studies will focus on a characterization of morphological and biochemical changes that precede, accompany, and follow cell division induced by traumatic insult to the lens in situ. The long-term goal of this study is the elucidation of the biological mechanisms which control cell division, growth and tissue repair in the ocular lens.